1. Experiments were carried out using intracellular recording techniques on hippocampal neurons maintained in culture to determine if populations of hippocampal neurons could be induced to develop spontaneously recurring epileptiform discharges. This study demonstrates the conversion of normal hippocampal neurons in culture by a brief Mg(2+)-free treatment into a preparation of cells that permanently manifested recurrent, spontaneous seizure discharges. These electrographic seizure discharges illustrated the same electrographic properties seen in human epilepsy and were observed for the life of the culture. 2. The epileptic activity was shown to occur synchronously in populations of neurons and to be controlled by clinically useful anticonvulsant drugs. 3. This new cell culture model of epileptic activity provides a powerful tool to investigate the molecular mechanisms underlying the induction, maintenance, and termination of this "epileptic condition" in vitro and demonstrates that neuronal networks in culture can be transformed to manifest permanently spontaneous recurrent electrographic seizures.